The present invention relates to the art of making chewable comestible dosage units, such as tablets, which disintegrate quickly in the mouth.
Dosage units in the form of tablets are usually prepared by compressing a formulation containing a medicinal substance or drug and other ingredients, such as excipients selected for properties which facilitate production and use of the tablet. There are currently three known basic methods for preparing tablet granulations. These are wet granulation, dry granulation and direct compression. Both wet and dry granulations involve the formation of an agglomerate for feeding to a die cavity. Direct compression usually involves compressing a powder blend of an active ingredient with suitable excipients.
Wet granulation is an expensive process because it requires many processing steps and involves considerable material handling equipment. Consequently, the process requires both energy and substantial space which should be environmentally controlled.
Generally, free water and heat are inimical to active ingredient. Wet granulation procedures involve water and/or heat. Therefore, it is desirable to provide a method for making tablets in the substantial absence of heat and free water in order to enhance the survival of active ingredients incorporated in the tablet.
Dry granulation refers to the granulation of a powder mixture by compression without the use of heat and solvent. Dry granulation is used when wet granulation is not available because the drug is sensitive to moisture or heat.
Dry granulation has many disadvantages. It requires a specialized heavy-duty tablet press to form the slug; it does not permit uniform color distribution as can be achieved with wet granulation, where dye can be incorporated into the binder liquid; the pressure roll press cannot be used with insoluble drugs because this may retard the dissolution rate; and the process tends to create dust thereby increasing the potential for cross-contamination.
Direct compression tabletting has the least amount of steps. Direct compression is used in a process by which tablets are compressed directly from powder blends of the active ingredient and suitable excipients (including fillers, disintegrants, and lubricants).
Direct compression also has many technological limitations. These limitations include primarily obtaining sufficient flow, and obtaining bonding of particles to form a strong compressed tablet. Low-dose drugs are difficult to blend, that is, uniform distribution of the drug is not easily attained and unblending sometimes occurs during the compression stage. High-dose drugs do not lend themselves to direct compression because of poor flowability and poor compressibility. A typical example would be some of the antacid drugs, such as aluminum hydroxide and magnesium carbonate.
A disadvantage of all prior art processes is the production of fines usually associated with making compression tablets. In the prior art, preparation of particles for formulation of tablets by compression results in a noticeable amount of fines, i.e., very tiny particles on the order of 150 microns and less. These fines can interfere with operation of apparatus for feeding tabletting machines as well as the operation of the tabletting machines. This adds to the cost of production of the tablets.
Technology has been developed by the common owner of the present application and U.S. Pat. No. 5,654,003. The patent discloses a unique procedure in which compression tabletting can be simply and accurately manufactured by "fuse and compression" steps. Fusion is achieved by flash flow processing the tablet ingredients to provide shearform matrix masses which are subsequently compressed to form comestible compression units. This process includes advantages of wet and dry granulation and direct compression but does not have the disadvantages associated with these prior art procedures.
In commonly-owned patent U.S. Pat. No. 5,622,719, a rapidly-dissolving unit dosage and preparation and apparatus for making same are disclosed. The method disclosed therein includes mixing uncured shearform matrix material with an additive followed by lightly compressing the resulting mixture to form a dosage unit. The formed unit is subsequently cured by exposing to controlled ambient heat, moisture, and pressure.
Applicants' assignee also has several patents which relate to other unique delivery means. U.S. Pat. No. 4,855,326 discloses a fiber form of medicament-bearing product which can be compacted to form a sheet-like body. However, the compact body cannot be squeezed too much for fear of breaking the fibrous mass.
In U.S. Pat. No. 4,997,856, a wafer-like structure is disclosed in which a medicament is distributed on or through spun fibers which are then chopped by passing through a conventional "food grinder" (Hobart hamburger grinder). The enclosed volume of the end product is less than 30%, and preferably less than 15% of the as-spun volume of floss.
The use of compacted spun fibers is also disclosed in U.S. Pat. Nos. 5,034,421 and 5,096,492.
While the procedure described in U.S. Pat. No. 5,622,719 discloses a technique for making a rapidly dissolving dosage unit, none of the other procedures provide a technique for forming a dosage unit which quickly disintegrates in the mouth of the consumer, but which can be conveniently manufactured for shipment and sales.